The overall goal of this project is to study the kinetics and mechanisms of milk secretion by examining a variety of conditions and agents which may influence the quality and quantity of milk-specific products secreted by mammary epithelial cells. These mammary epithelial cells are unique in their ability to simultaneously synthesize and secrete triglycerides containing medium-chain length fatty acids, casein, alpha-lactalbumin and lactose. Methods are now available for obtaining and culturing as monolayers or suspensions relatively pure populations of mammary epithelial cells free of other cell types, e.g., fibroblasts, adipose cells and blood cells. Quantitative assays have also been developed in our laboratory for the study of synthesis and secretion of milk-specific rats (triglycerides), proteins (casein, alpha-lactalbumin) and carbohydrates (lactose) by isolated mammary epithelial cells in vitro. Accordingly, it is now feasible to analyze quantitatively for the first time at the cell level details of secretory responses by mammary epithelia to selected components added to the culture medium and to assess the importance of these compounds in vitro as an indication of an in vivo effect. Therefore, our specific objectives will be to (a) clearly define the kinetics of milk secretion in freshly isolated or cultured mammary epithelial cells from pregnant and lactating mice and guinea pigs, (b) obtain information on the mechanisms involved in the secretory process(es) and (c) investigate the ability of various nutrients, vitamins, hormones and pharmacologic agents to alter the normal secretory response. BIBLIOGRAPHIC REFERENCES: Feldman, M.K., R. C. Foster and D.L. Wong. (1977). Effect of retinyl acetate on mammary epithelial cells. Proc. Amer. Cancer Res, in press. Foster, R.C., M.K. Feldman and D.L. Wong. (1977). Stimulated uptake of thymidine by retinoids in primary cell cultures of mouse mammary epithelium. In vitro, in press.